The standard method for searching for new chemical compounds which can effectively modulate biological processes employs the screening of pre-existing compounds in assays which have been designed to test particular properties of the compound being screened. Similarly, in designing compounds having desired physiochemical properties for general chemical applications, numerous compounds must be individually prepared and tested.
To reduce the time and expense involved in preparing and screening a large number of compounds for biological activity or for desirable physiochemical properties, technology has been developed for providing libraries of compounds for the discovery of lead compounds. Current methods for generating large numbers of molecularly diverse compounds focus on the use of solid phase synthesis. The generation of combinatorial libraries of chemical compounds by employing solid phase synthesis is well known in the art. For example, Geysen, et al. (Proc. Natl. Acad. Sci. USA, 3998 (1984) describe the construction of multi-amino acid peptide libraries; Houghton, et al. (Nature, 354, 84 (1991) and PCT Patent Pub. No. WO 92/09300) describe the generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery; Lam, et al. (Nature, 354, 82 (1991) and PCT Patent Pub. No. WO 92/00091) describe a method of synthesis of linear peptides on a solid support such as polystyrene or polyacrylamide resin.
The growing importance of combinatorial chemistry as an integral component of the drug discovery process has spurred extensive technological and synthetic advances in the field (Thompson, L. A.; Ellman, J. A. (1996) Chem. Rev. 96,555-600). Founded in peptide synthesis devised by Merrifield, solid phase chemistry has emerged as the preeminent method for construction of small molecule combinatorial libraries (see e.g. Merrifield, R B. (I 963) J. Am. Chem. Soc. 85, 21492154; (a) Terrett, N. K.; Gardner, M.; Gordon, D. W.; Kobylecki, R. J.; Steele, J. (1995) Tetrahedron 51 (30), 8135-8173. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. (1994) J. Med Chem. 37,1385-1401.).
Unfortunately, the generation of chemical compounds for combinatorial chemical libraries is a labor intensive process. Working with numerous reaction vessels concurrently is very difficult and time consuming. In the past, multiple solid phase reactions were conducted manually by filling a test tube with reaction media, heating it in a hot oil bath, and agitating the media a rotating magnetic stir bar. Draining was accomplished by pouring the contents of the test tube through a filter. As synthesis often required numerous steps, back and forth operation between reacting and draining procedures was physically burdensome and potentially exposed the reaction mixture to air contamination.
Although certain chemical synthesizing devices are known in the art, these devices fail to provide the qualities desired for efficiently generating large numbers of chemical compounds. There remains a need for a device which can provide heating, cooling, mixing, adding of solid reagents during synthesis, easy draining, and/or simultaneous filling of a plurality of reaction vessels in a inert atmosphere.